Experimental and DFT studies on the regioselective methanolysis of 5-azido-9-oxabicyclo[6.1.0]nonan-4-yl 4-nitrobenzoate isomers

• İlknur Polat,
• Selçuk Eşsiz and
• Emine Salamci

Beilstein J. Org. Chem. 2026, 22, 547–556, doi:10.3762/bjoc.22.40

• ][13][14][15][16][17][18][19]. The ring-opening reactions of bicyclic epoxides are of significant importance and scientific interest due to their high ring strain, their strategic role in the construction of complex molecular architectures, and their utility in the synthesis of natural products

• , pharmaceutical compounds, and chiral ligands. The Lewis acid-catalyzed ring-opening reaction of cyclohexene oxide by MeZH (Z = O, S, and NH) is well known [20]. However, studies on large-sized bicyclic epoxides remain relatively limited in the published literature. In our previous study, we performed the ring

• ring-opening reaction of the epoxides 9 with HCl(g) in MeOH resulted in the formation of chlorohydrin-azidobenzoate isomers 10 and 11 in a total yield of 96% (Scheme 2). Then, for full characterization of the structures of the obtained products, the mixture of chlorohydrins was converted into the

Modern synthetic pathways towards eribulin and its subunits

• Sebastian Dominik Graf

Beilstein J. Org. Chem. 2026, 22, 495–526, doi:10.3762/bjoc.22.37

• , intramolecular ring opening of epoxide 98 and metathesis led to target 104 with high regio- and stereoselectivity. A novel approach towards C1–C10 fragment of 1 was reported by Kathravath and co-workers (Scheme 11) [87]. From ʟ-ascorbic acid (108), protection of the diol motif and treatment with H2O2, then EtI

• -workers assembled 276 via simple ring opening of 275`s oxetane moiety and no cooling and intermediate purification were necessary. These practical improvements are particularly important for the large-scale synthesis of 1. Furthermore, every step up to 292 was carried out in kg amounts using only

• known procedure [79]. Acidic treatment in MeOH and subsequent addition of MeLi furnished full acetal 301 (Scheme 35). Treatment with Tf2NPh yielded an intermediate enol triflate, which underwent a β-hydride elimination towards allene 302 upon addition of Pd2(dba)3. Next, ring opening of the full acetal

Dialkylaminoalkylation of β-ketosulfones via ring-opening of 3-sulfonylpyrrolidines

• Evgeny M. Buev,
• Alexander V. Pavlushin,
• Vladimir S. Moshkin and
• Vyacheslav Y. Sosnovskikh

Beilstein J. Org. Chem. 2026, 22, 383–389, doi:10.3762/bjoc.22.26

• of the quaternary ammonium salt in the presence of a O-, S- or N-nucleophile with cesium carbonate leads to a retro-Claisen reaction, ring-opening and Michael addition. The resulting novel 4-Nu-3-sulfonylbutan-1-amines are isolated in moderate to excellent overall yields. The reduction of the

• quaternary ammonium salt of 3,3-dibenzoylpyrrolidine, derived from dibenzoylmethane, undergoes ring-opening in the presence of a nucleophile and sodium methoxide via a retro-Claisen reaction [33]. This process yields 4-(dimethylamino)-2-heteromethyl-1-phenylbutan-1-one scaffold V (EWG = COPh; Y = OR, SR, NR

• domino-process consists in nucleophilic addition of the alcohol, mercaptan or water (in case the reaction was performed in CH3CN) at the benzoyl group (Scheme 3). The subsequent ring-opening of the pyrrolidine ring can proceed via two possible pathways. First path is the tandem Grob-type fragmentation

Arene activation via π-bond localization: concepts and opportunities

• Paul Meiners,
• Julian J. Melder and
• Tobias Morack

Beilstein J. Org. Chem. 2026, 22, 257–273, doi:10.3762/bjoc.22.19

• , increases π-bond localization, rendering phenylenes more susceptible to hydrogenation, metal complexation, ring opening, and cycloaddition reactions [39]. Building on these intriguing studies and the ongoing renaissance of strain-release-driven catalysis [40], harnessing small-ring strain to drive

A mild and atom-efficient four-component cascade strategy for the construction of biologically relevant 4-hydroxyquinolin-2(1H)-one derivatives

• Dmitrii A. Grishin,
• Kseniia I. Sharkovskaia,
• Ilya G. Kolmakov,
• Daria A. Ipatova,
• Rostislav A. Petrov,
• Nikolai D. Dagaev,
• Dmitry A. Skvortsov,
• Maria G. Khrenova,
• Valeriy V. Andreychev,
• Sergei A. Evteev,
• Yan A. Ivanenkov,
• Roman L. Antipin,
• Olga А. Dontsova and
• Elena K. Beloglazkina

Beilstein J. Org. Chem. 2026, 22, 244–256, doi:10.3762/bjoc.22.18

• consistently confirmed the trend: greater electrophilicity is observed for the carbonyl carbon in pyranoquinoline, corroborating the experimental observations. Based on these results, the proposed mechanism of the multicomponent reaction involves initial lactone formation, followed by ring opening

Synthesis of diaryl phosphates using phytic acid as a phosphorus source

• Kazuya Asao,
• Seika Matsumoto,
• Haruka Mori,
• Riku Yoshimura,
• Takeshi Sasaki,
• Naoya Hirata,
• Yasuyuki Hayakawa and
• Shin-ichi Kawaguchi

Beilstein J. Org. Chem. 2026, 22, 213–223, doi:10.3762/bjoc.22.15

• [22] and as insecticides [23]. Particularly, phosphate diesters are among the most important synthetic catalysts, such as the Akiyama–Terada catalyst that serves as a chiral Brønsted acid catalyst [24][25] and promotes a variety of stereoselective reactions. Phosphate diesters also catalyze the ring

• -opening polymerization of some lactones [26][27] and are important for the syntheses of ionic liquids [28][29] and asymmetric phosphate esters. Furthermore, a novel metal extractant based on diaryl phosphate has recently been reported [30][31]. Phosphate esters are generally synthesized from phosphoryl

Highly electrophilic, gem- and spiro-activated trichloromethylnitrocyclopropanes: synthesis and structure

• Ilia A. Pilipenko,
• Mikhail V. Grigoriev,
• Olga Yu. Ozerova,
• Igor A. Litvinov,
• Darya V. Spiridonova,
• Aleksander V. Vasilyev and
• Sergey V. Makarenko

Beilstein J. Org. Chem. 2026, 22, 123–130, doi:10.3762/bjoc.22.5

• of ring opening or expanding [11][12][13]. Thus, known trichloromethyl-containing cyclopropanes can serve as precursors for hard-to-access halogenated β,γ- and γ,δ-unsaturated esters [14][15]. Nitrocyclopropanes are known as highly electrophilic substrates and can form a carbanion stabilized by the

Advances in Zr-mediated radical transformations and applications to total synthesis

• Hiroshige Ogawa and
• Hugh Nakamura

Beilstein J. Org. Chem. 2026, 22, 71–87, doi:10.3762/bjoc.22.3

• for further development in this area. In 2022, Ota and Yamaguchi et al. reported the zirconocene-catalyzed ring-opening of epoxides using Cp₂Zr(OTf)2·THF (Scheme 5) [4]. Traditionally, such transformations are carried out with low-valent titanium catalysts, which typically proceed via more substituted

• unsymmetrical epoxides (Scheme 5B). Both monosubstituted epoxides 23a–e and di- and trisubstituted epoxides 23f–h underwent ring opening with regioselectivity opposite to that observed in conventional systems, affording the corresponding alcohols. Moreover, the method was successfully applied to complex

• experiments, coordination of thiourea 26 to the Zr center was suggested. This effect is considered to have tuned the reactivity of the Zr-catalyst, thereby having a positive effect on the reaction process. Finally, the regioselectivity of epoxide ring opening was compared between low-valent titanocene and

Synthesis and applications of alkenyl chlorides (vinyl chlorides): a review

• Daniel S. Müller

Beilstein J. Org. Chem. 2026, 22, 1–63, doi:10.3762/bjoc.22.1

• HIV-1 non-nucleoside reverse transcriptase inhibitor, they aimed to improve the preparation of compound 19, whose yield had previously been limited to 22% following a similar route. They noticed that in situ-generated species such as POCl3 or HCl triggered ring opening of dichloride 15 to produce a

• compounds 15 and 18 without contamination with E- or Z-16 isomers (Scheme 4). Additionally, it was found that several aqueous work-up procedures induced ring opening of compounds 17 and 18. Ultimately, steam distillation directly from the reaction mixture afforded a toluene solution of compounds 15 and 18

• oxidation/halogenation reaction of allylic alcohols, as recently reported by Chisholm and co-workers (Scheme 36) [137]. Their approach involves oxidation of the allylic alcohol under Moffatt–Swern conditions, followed by halogenation of the resulting enone to generate a chloronium ion. Subsequent ring

Visible-light-driven NHC and organophotoredox dual catalysis for the synthesis of carbonyl compounds

• Vasudevan Dhayalan

Beilstein J. Org. Chem. 2025, 21, 2584–2603, doi:10.3762/bjoc.21.200

• -rich and electron-poor substituents. This reaction was carried out between arylcyclopropanes 5 and acyl fluoride 4 in the presence of NHC (10 mol %) and 4CzIPN (5 mol %). Mechanistic studies showed that the cascade proceeds via nucleophilic ring-opening of a cyclopropyl radical cation D with subsequent

• amide via dual catalysis. Visible-light promoted cooperative NHC/photoredox catalyzed ring-opening of aryl cyclopropanes. NHC-catalyzed benzylic C–H acylation by dual catalysis. NHC/photoredox-catalyzed three-component coupling reaction for the preparation of γ-aryloxy ketones. NHC-catalyzed silyl

Recent advances in total synthesis of illisimonin A

• Juan Huang and
• Ming Yang

Beilstein J. Org. Chem. 2025, 21, 2571–2583, doi:10.3762/bjoc.21.199

• epoxide ring-opening afforded 71. To install the all-carbon quaternary center at C5, compound 71 was treated with t-BuOK and MeI, enabling the deprotonation of the α,β-unsaturated aldehyde and methylation at C5; this step also facilitated protection of the secondary alcohol. The aldehyde was reduced in

Total syntheses of highly oxidative Ryania diterpenoids facilitated by innovations in synthetic strategies

• Zhi-Qi Cao,
• Jin-Bao Qiao and
• Yu-Ming Zhao

Beilstein J. Org. Chem. 2025, 21, 2553–2570, doi:10.3762/bjoc.21.198

• compound 19. This intermediate is converted to lactone 20 via base-promoted Grob fragmentation followed by acid-mediated MOM deprotection. Epoxidation of the C10–C11 double bond in 20, lactone hydrolysis-promoted epoxide ring opening, and inversion of the C10 hydroxy configuration, yield the key

• successfully accomplished via an epoxide ring-opening/tandem lactonization/olefin hydration sequence. In total, 12 consecutive redox manipulations (7 oxidations and 5 reductions) established all stereocenters, with subsequent functional group transformations completing the total synthesis of garajonone (8

• , the bis-epoxy ketone exhibited distinct reactivity under ring-opening conditions compared to mono-epoxy substrates, presumably due to steric constraints. Leveraging the directing ability of the C10 hydroxy group, stereospecific Mukaiyama hydration of the C6–C7 double bond was achieved, furnishing

Isoorotamide-based peptide nucleic acid nucleobases with extended linkers aimed at distal base recognition of adenosine in double helical RNA

• Grant D. Walby,
• Brandon R. Tessier,
• Tristan L. Mabee,
• Jennah M. Hoke,
• Hallie M. Bleam,
• Angelina Giglio-Tos,
• Emily E. Harding,
• Vladislavs Baskevics,
• Martins Katkevics,
• Eriks Rozners and
• James A. MacKay

Beilstein J. Org. Chem. 2025, 21, 2513–2523, doi:10.3762/bjoc.21.193

• addition of the acyl chloride to excess 9 was important to avoid forming bis-acylation of the phenylenediamine. The carboxylic acid 13 was formed using a microwave-promoted ring opening of glutaric anhydride (11) and benzyl-protected PNA backbone 12 [38]. A series of optimizations was performed in a

Transformation of the cyclohexane ring to the cyclopentane fragment of biologically active compounds

• Natalya Akhmetdinova,
• Ilgiz Biktagirov and
• Liliya Kh. Faizullina

Beilstein J. Org. Chem. 2025, 21, 2416–2446, doi:10.3762/bjoc.21.185

• product of cyclohexane ring opening (Scheme 26). A decrease in the methanol content of the mixture to 0.5% was accompanied by a slowdown in the process and the appearance of keto enol 149 in solution. Replacing methanol with isopropanol under these conditions resulted in the formation of isopropyl esters

• products of epoxide ring opening. It should be noted that the position of the epoxy ring in the 6-membered ring has a major influence on the composition of reaction products. Catalysts only affect the yield of the reaction. A striking confirmation of this is the work of Berteina-Raboin and co-workers [87

The high potential of methyl laurate as a recyclable competitor to conventional toxic solvents in [3 + 2] cycloaddition reactions

• Ayhan Yıldırım and
• Mustafa Göker

Beilstein J. Org. Chem. 2025, 21, 2389–2415, doi:10.3762/bjoc.21.184

• scaffolds. From the standpoint of organic chemistry, it is evident that these compounds can be efficiently converted into a variety of versatile organic intermediates through the application of ring-opening reactions [49][50][51][52]. In addition to the aforementioned useful properties, the current methods

Synthetic study toward vibralactone

• Liang Shi,
• Jiayi Song,
• Yiqing Li,
• Jia-Chen Li,
• Shuqi Li,
• Li Ren,
• Zhi-Yun Liu and
• Hong-Dong Hao

Beilstein J. Org. Chem. 2025, 21, 2376–2382, doi:10.3762/bjoc.21.182

• , although the corresponding enone product was not isolated. Facing a dead-end, the synthetic route to precursor 14 needed to be revised. From 15, after sodium methoxide-mediated ring opening of lactone, the Fráter–Seebach alkylation [39][40][41] was applied to afford β-hydroxy ester 18. At this stage, the

Recent advances in Norrish–Yang cyclization and dicarbonyl photoredox reactions for natural product synthesis

• Peng-Xi Luo,
• Jin-Xuan Yang,
• Shao-Min Fu and
• Bo Liu

Beilstein J. Org. Chem. 2025, 21, 2315–2333, doi:10.3762/bjoc.21.177

• can further undergo ring-opening or rearrangement reaction to assemble complex molecular frameworks. Additionally, quinone photoredox reactions involving single-electron transfer (SET) processes provide novel strategies for the stereoselective synthesis of useful structures such as spiroketals. This

• -hydroxy-β-lactams or 2-hydroxycyclobutanones can function either as inherent structural motifs in target natural products or as strained reactive intermediates, facilitating C–H functionalization via four-membered ring opening [6][7][8][9][10][11]. Quinones display distinct photochemical reactivities

• -chloroperoxybenzoic acid) induced epoxidation, which was then followed by a Meinwald rearrangement to accomplish aldehyde 7. From 7, a sequence involving silyl enol ether formation, Simmons−Smith cyclopropanation, and acid-mediated regioselective ring-opening installed the C8 quaternary methyl group in 10. Subsequent

Pathway economy in cyclization of 1,n-enynes

• Hezhen Han,
• Wenjie Mao,
• Bin Lin,
• Maosheng Cheng,
• Lu Yang and
• Yongxiang Liu

Beilstein J. Org. Chem. 2025, 21, 2260–2282, doi:10.3762/bjoc.21.173

• and hydrogen elimination then occurred, affording 3-azabicyclo[4.1.0]hepta-2,4-diene derivatives 156. In contrast, when the temperature was raised to 110 °C, intermediate 155 underwent a 6π electrocyclic ring-opening, which was trapped by in situ-generated cyanide ions to form 4,5-dihydro-3H-azepines

C2 to C6 biobased carbonyl platforms for fine chemistry

• Jingjing Jiang,
• Muhammad Noman Haider Tariq,
• Florence Popowycz,
• Yanlong Gu and
• Yves Queneau

Beilstein J. Org. Chem. 2025, 21, 2103–2172, doi:10.3762/bjoc.21.165

• reported by Strizhov et al. [125]. The liable equilibrium transformation requires precisely pH-controlled conditions. In neutral medium, the furanone is in the form of its cis tautomer, while upon a slight increase in the pH, its cyclic original tautomer undergoes a ring opening with the formation of

• catalyst could be recovered and reused five times without significant loss of activity (Scheme 51) [179]. Furfural can be converted to 2-pentanone via simultaneous hydrodeoxygenation, ring-opening, and hydrogenation reactions under catalysis by a bimetallic Cu–Ni/SBA-15 catalyst in a fixed-bed continuous

• mechanism involves a ring opening of GVL at the Brønsted acidic sites, while the β-proton abstraction occurs on the support surface basic sites [232]. Catalytic aerobic oxidation of levulinic acid towards dicarboxylic acids is a way to obtain monomers for the manufacture of biobased polymers. For example

The application of desymmetric enantioselective reduction of cyclic 1,3-dicarbonyl compounds in the total synthesis of terpenoid and alkaloid natural products

• Dong-Xing Tan and
• Fu-She Han

Beilstein J. Org. Chem. 2025, 21, 2085–2102, doi:10.3762/bjoc.21.164

• operation including azide–alkene dipolar cycloaddition, irradiation of the resulting triazoline to aziridine 80 and in situ ring opening followed by deacetylation achieved the first total synthesis of (−)-hunterine A (14). On the other hand, aza-Cope/Mannich reaction of 78 produced imine intermediate 81

• intramolecular Diels–Alder reaction generated tricyclo[3.2.1.02,7]-octene 113. A two-step transformation including HAT hydrogenation and acetal C–H oxidation with RuCl3/NaIO4, 113 was converted into ketoester 114. The TFA-mediated C13–C15 bond cleavage of 114 proceed smoothly to give ring-opening products, which

• underwent dehydration with Martin′s sulfurane to afford the known intermediate 115 [83] and terminal alkene 116 (C12–C13 bond-cleaved byproduct). Thus, the formal total synthesis of (−)-platencin (24) was achieved. On the other hand, epoxidation of 113 followed by acid-mediated regioselective ring-opening

Understanding the origin of stereoselectivity in the photochemical denitrogenation of 2,3-diazabicyclo[2.2.1]heptene and its derivatives with non-adiabatic molecular dynamics

• Leticia A. Gomes and
• Steven A. Lopez

Beilstein J. Org. Chem. 2025, 21, 2007–2020, doi:10.3762/bjoc.21.156

• synthesis of strained compounds such as bicyclo[1.1.0]butane (BCB) and bicyclo[2.1.0]pentane (housane). The energy stored in strained σCC bonds of BCB and housane makes them important building blocks in the synthesis of complex molecular structures. BCBs have been employed in ring-opening reactions with

Preparation of spirocyclic oxindoles by cyclisation of an oxime to a nitrone and dipolar cycloaddition

• Beth L. Ritchie,
• Alexandra Longcake and
• Iain Coldham

Beilstein J. Org. Chem. 2025, 21, 1890–1896, doi:10.3762/bjoc.21.146

• that can be explored for its ability to undergo dipolar cycloaddition chemistry. Results and Discussion The oxindole core was prepared from isatin following known chemistry to give the spirocyclic epoxide 1 (Scheme 2) [28]. This was subjected to regioselective ring-opening with allyltrimethylsilane in

Photoswitches beyond azobenzene: a beginner’s guide

• Michela Marcon,
• Christoph Haag and
• Burkhard König

Beilstein J. Org. Chem. 2025, 21, 1808–1853, doi:10.3762/bjoc.21.143

• to a low activation energy barrier for the ground-state ring-opening [127]. Heterocycles with lower aromatic stabilisation energies are less susceptible to thermal ring-opening (Figure 21). The substituent nature of the aromatic groups was also demonstrated to influence the thermal stability

Catalytic asymmetric reactions of isocyanides for constructing non-central chirality

• Jia-Yu Liao

Beilstein J. Org. Chem. 2025, 21, 1648–1660, doi:10.3762/bjoc.21.129

• lactones with carbon nucleophiles. The success lies in the tandem enantioselective ring-opening of lactones with α-acidic isocyanides, followed by a rapid cyclization driven by aromatization, overcoming the long-standing stereochemical leakage problem caused by the undesired lactol formation [45

• ]. Encouraged by the above results, we turned our attention to biaryl lactams [49]. However, in this case, the inherent resonance stability of the amide bond makes the ring-opening process rather challenging. To solve this problem, we envisioned that a cooperative catalytic system merging silver catalysis and

3-Aryl-2H-azirines as annulation reagents in the Ni(II)-catalyzed synthesis of 1H-benzo[4,5]thieno[3,2-b]pyrroles

• Julia I. Pavlenko,
• Pavel A. Sakharov,
• Anastasiya V. Agafonova,
• Derenik A. Isadzhanyan,
• Alexander F. Khlebnikov and
• Mikhail S. Novikov

Beilstein J. Org. Chem. 2025, 21, 1595–1602, doi:10.3762/bjoc.21.123

• method for the synthesis of 3-arylbenzo[4,5]thieno[3,2-b]pyrroles has been developed via pyrrole ring annulation to the aromatic benzo[b]thiophene system, using 3-arylazirines as a N‒C=C synthon. The reaction is catalyzed by Ni(hfacac)2 and proceeds through the azirine ring opening across the N=C3 bond

• to the azirine C=N bond, followed by cyclization and the aziridine ring opening into the [3 + 2] cycloaddition product 5 (Scheme 3). It is noteworthy that the annulation proceeds via the azirine N‒C3 bond cleavage. Elimination of the methoxycarbonyl group most likely occurs under the action of

• proceeds through azirine ring opening across the N–C3 bond. Azirines with both electron-donating and electron-withdrawing C3-aryl substituents tolerate the reaction conditions, and give the annulation products in high yields. The synthesized 3-aryl-1H-benzo[4,5]thieno[3,2-b]pyrroles can be effectively